The main objective of the proposed study is to determine the mechanism(s) of action of gaseous anesthetics. In spite of intense investigation and their immense clinical importance very little is known concerning the mechanisms by which these compound interact with neural tissue, especially within the central nervous system. This is partly because of the complexity of the mammalian brain which has prevented measurements of precise membrane functions from being made under well-controlled experimental conditions. By using molluscan giant neurons as a model of the more complex vertebrate system it is possible to study specific neural processes in isolation one from the other, namely endogenous membrane currents, direct synaptic linkages and membrane receptors to putative transmitters. This project will examine the predictions of two general hypotheses of anesthetic action on several different neuronal functions from these three groups in an attempt to determine 1) if anesthesia results from a disruption of specific membrane components and the functions they control, and 2) if pressure reversal occurs at the same site as the anesthetic effect. The prediction is that discrete membrane functions will show differing sensitivities and be affected at differing rates from each other and that pressure reversal will show a selective effect on the specific functions. These events will be followed using voltage clamp techniques, iontophoretic application of transmitters and a specially designed high pressure chamber for the application of inert gases at high pressure and for the studies of pressure reversal.